Discussion
Total splenectomy is a proven and effective method for the treatment of patients with moderate to severe HS3. The spleen is the largest peripheral lymphoid organ in the body, it is an indispensable immune barrier when the body receives external viruses and bacteria. The absence of spleen might lead an infection outbreak. For pediatric patients, possible postoperative aggressive complications such as OPSI and surgical trauma have been a long-term problem for physicians and patients. In 1973, Maddison7 proposed splenic artery embolization as a minimally invasive procedure for the treatment of hypersplenism that solves the problem of severe trauma. Spigos8 et al. developed transcatheter partial splenic embolization (PSE) in adult HS to preserve the immune function of the spleen5,6. However, PSE has not been widely promoted in pediatric patients because of the poor controllability of the extent of PSE embolization.
In our study, all the patients had moderate or severe HS. The success rate of splenectomy and SPSE was 100%. Postoperative hemolysis was significantly improved, no further transfusions were performed in our patients. Previous studies had shown that PSE was effective in reducing the degree of hemolysis while maintaining the phagocytic function of the splenic remnant, and the selective destruction of the spleen to defective red blood cells5. In this study, based on the unique anatomy of the spleen and splenic artery, selective embolization of grade 2 to grade 3 arterial branches was performed in the spleen by intraoperative angiography. Measuring the embolic artery blood flow velocity and performing a comprehensive pre-evaluation of the extent of splenic embolization to achieving an accurate prediction of splenic embolic volume. The extent of spleen volume that examined by CT before and after embolization was 75% to 90%, which was consistent with the pre-evaluation results. Therefore, we believe the degree of splenic embolization can be precisely controlled by SPSE to achieve a therapeutic effect of reducing hemolysis.
The white marrow of the spleen is an important component of the lymphoid tissue in the body (Approximately 25%). It has germinal centers which dominated by early B lymphocytes and plasma cells. Therefore, total splenectomy can lead to a significant reduction in antibody production. When foreign antigens are appeared in the circulation, the spleen provides an essential place for the immune response9. In this study, SPSE can effectively reduce the volume of the spleen and maintain the immune function of the splenic white marrow to some extent. The mild elevation of the complement system compared to the preoperative period was considered an effect possibly relate to surgical embolization10,11. The complement system exerts innate immune by lysing or killing of bacteria, modulating phagocytosis or participates in antibody-mediated specific immune responses. Our study also showed that all splenic immune functions were maintained in the normal range after SPSE and no surgery-related infection of SPSE during the follow-up period. Thus, we demonstrated SPSE had a substantial improvement in maintaining normal immune function than total splenectomy. We are aware that the younger the patients with HS diagnosis, the severer the symptoms of hemolytic anemia may have. Considering the risk of post-splenectomy fulminant infection, many patients with total splenectomy was significantly older. We believed SPSE preserves normal immune function while treating HS, offers the possibility of surgery in earlier ages and reduces the complications for patients with HS.
All the post-embolization syndromes in this study are minor and controllable, it mainly manifested by abdominal pain, fever and vomiting. Most patients’ symptoms resolve within 1 week after surgery. Previous studies have shown that common complications of total splenectomy include postoperative infection, OPSI, surgical bleeding, injury of adjacent organs and venous thromboembolism (VTE)2,12,13. The most serious complications of PSE are abdominal infection and spleen abscess formation, which is deadly for patients in severe cases14. The cause of spleen abscess formation includes excessive embolization which leads liquefied necrosis of a large amount of spleen tissue and secondary bacterial infection. There are two possible sources of bacteria, one of them is interventional contamination, the other is that, the enteric-derived bacteria which retained in the portal venous system reverse into the spleen since the slow speed of flow in the splenic vein after massive embolization of the splenic parenchyma15. However, there is no patient had a splenic abscess in this study. The reason to do this study is as following. Firstly, the number of patients is still small. Secondly, SPSE achieved the purpose that accurately embolization by the accurate selection of secondary arteries and narrowing the possibility of infection caused by stagnation of splenic vein blood flow which is the result of over embolization of splenic artery trunk. Thirdly, the minified dosage of embolic agent during treatment also indirectly diminishes the risk of contamination. The fact that there is not any expose of significant flow stagnation or reflux in the splenic artery angiogram after SPSE had been confirmed by the color ultrasonography of the blood flow of splenic vein 3 days after the procedure. In addition, triple cephalosporin was intravenously applied within 48 hours postoperatively. Since these prophylactic anti-infection actions were actively performed, the risk of splenic infection was minimized by avoiding possible intraoperative contamination and postoperative enterogenic infection to the greatest extent.
A few reports of previous study shown the growth of residual accessory spleen after total splenectomy16, or growth of residual spleen after partial splenectomy trigger recurrence of anemia which requires secondary surgery17,18. In a long-term follow-up study of partial splenectomy19, mild and moderate hemolysis may be a long term symptoms after partial splenectomy, and a small number of patients may be at risk of secondary gallstones and hemolytic anemia. In our observed SPSE patients with a median follow-up time of 19 months (8-26 months), there is no cases of hemolytic anemia which requires transfusion therapy, only a few children have mild hemolysis and all patients with SPSE recovered well after surgery. We believe the better results were mainly becauseonly small portion of the upper splenic (10%-20%) were preserved by the accurate control of embolization, moreover, the growth of the normal residual spleen was effectively limited by the blockage of diaphragm and embolized spleen. In fact, since we preserved the splenic artery trunk upfront, there is an opportunity to do another embolization as re-intervention if symptomatic recurrence of anemia appeared at later stage. The shortage of this study is the short follow-up period. Hence, long-term follow-up should be applied to clarify the dynamic changes of spleen volume and hemolysis after embolization.
In conclusion, SPSE is a feasible, safe and effective alternative to splenectomy for childhood hereditary spherocytosis. SPSE may have greater advantages on expanding the age range of surgery, reducing the severity of surgical trauma, and minimizing the possibility of infection. However, a longer follow-up period, a larger sample size, and applying other indications such as hypersplenism, are mandatory for the further assessment of SPSE.